Minimally invasive tests for the detection and monitoring of malignancies are urgently needed worldwide to reduce the morbidity and mortality caused by cancer. While promising, blood-based proteonomic assays have yet to be clinically validated for many common human cancers. Accordingly, new approaches are being investigated that will likely complement or improve on current strategies. In particular, microRNAs (miRNAs) have gained considerable attention as potentially predictive biomarkers for a number of disorders. This Phase I research project will evaluate the feasibility of rapid, label-free identification and quantification of miRNAs from blood samples using a novel ultra-sensitive detection technology known as Surface Plasmon Enhanced Common Path Interferometry (SPE-CPI). SPE-CPI differs from standard Surface Plasmon Resonance (SPR) detection methods, such as Biacore, in that it combines the high sensitivity of SPR with the higher stability and lower noise of a CPI single-beam path. SPE- CPI also allows for the simultaneous monitoring of multiple species of miRNA in a single sample. During Phase I, SPE-CPI based protocols for measuring cancer-related miRNAs in the presence of serum will be identified and qualified. Specificity and limit of detection will be critical parameters for this proof-of-feasibility study. Further, using the optimized SPE-CPI methods, we will evaluate the potential of SPE-CPI as a diagnostic tool for the detection of miRNAs using serum samples from patients with lung cancer versus healthy individuals. If successful, this research will be a major step forward in new diagnostic strategies for cancer and possibly other diseases that may be modulated by miRNA. Advancements in label-free sensing technologies will also open broader applications for the measurement of low abundance proteins, protein- protein interaction studies, infectious disease detection, biowarfare pathogen detection, protein- drug interactions, food safety, detection of chemical pollutants, and the like. The SPE-CPI instrument that will be evaluated in these studies is small, inexpensive, and requires minimal sample manipulation for analysis. Affordable, easy-to use detectors for rapid screening at point of care facilities, i.e. doctors'offices, would be a significant breakthrough in the health care industry. PUBLIC HEALTH RELEVANCE: This Small Business Innovation Research (SBIR) Phase I project will evaluate an ultra-sensitive detection technology for the non-invasive multiplex quantification of lung cancer biomarkers in serum samples. If successful, this research will be a major step forward in a new strategy for point of care diagnosis of cancer and other diseases. Advancements in biosensor technologies will also open broader applications for the measurement of low abundance proteins, protein-protein interaction studies, infectious disease detection, biowarfare pathogen detection, protein-drug interactions, vaccine development, food safety, detection of chemical pollutants, and the like.